Within certain cells, peptides from foreign or self antigens are bound intracellularly to MHC molecules and are then brought to the cell surface where the peptide and the presenting MHC molecules are recognized together as a complex by receptors on T lymphocytes. Generally, MHC type I molecules present endogenously synthesized antigen and MHC type II molecules present exogenous antigen. Peptide fragments of intracellular infectious organisms are transferred into the endoplasmic reticulum to bind to MHC class I molecules shortly after synthesis. Peptide fragments of endocytosed, extracellular antigen are created by proteolysis in a post-Golgi processing compartment where the fragments then become associated with MHC class II molecules. Most cells are capable of processing and presenting peptide fragments by MHC class I molecules, and specialized classes of antigen presenting cells also present exogenous antigen by the MHC class II pathway. For example, macrophages take up and present antigen to T cells which mature into helper or killer cells, and virgin B cells bind antigens to their surface immunoglobulins and then endocytose, digest and present fragments of that antigen via their MHC class II molecules to helper T cells. Those helper T cells release lymphokines and give direct intercellular molecular signals which stimulate the B cells to proliferate and mature into immunoglobulin producing plasma cell "factories". Antigen presentation by MHC class II molecules is crucial to initiation of many protective immune responses and to the origin of autoimmune responses.
An important regulator of antigen charging of the MHC class II .alpha.,.beta. chain complex is the I.sub.i protein. This protein joins the MHC class II .alpha.,.beta. chains at synthesis and is lost in a post-Golgi compartment where it might be digested with the same proteases which generate peptide fragments from foreign antigens. Blocking of the peptide binding site on the MHC class II .alpha.,.beta. chains until the digestion of I.sub.i in the antigen processing compartment, presumably limits autoantigen presentation. That is, since MHC class II molecules can present endogenously synthesized, viral determinants the circumstances of binding might reflect either (1) transport of such determinants into the post-Golgi antigen binding compartment from the cytoplasm across the membrane of that compartment, or (2) transport of such peptides into the endoplasmic reticulum and `premature` binding to MHC class II molecules upon `early` release of I.sub.i or flow of such peptides perhaps in protected complexes to the post-Golgi antigen binding compartment.